Until recent years, assessment of the cerebrovascular status in intensive care unit (ICU) patients has been confined to the determination of cerebral perfusion pressure (CPP) using intracranial pressure (ICP) measurements. New techniques for cerebrovascular assessments include thermal diffusion flowmetry (TDF), which has been used in the ICU owing to the availability of a new generation of probes. The instrument is compact, functions in real time, and provides regional cerebral blood flow (rCBF) data in absolute units (e.g., ml/100 g/min). However, intracranial placement requires intraoperative access which limits monitoring to operative cases. Other obstacles include: suboptimal coupling between the gold plates and cortical surface; repeated local heating of cortical tissue; and only mean values are given without the capacity to visualize a waveform; and as mentioned rCBF is monitored as opposed to the microcirculation (i.e., 1CBF).
Another new technology is transcranial Doppler (TCD) velocimetry in which instruments are equipped with continuous monitoring probes that measure the velocity of blood flow in large intracranial conductance vessels. Weber et al., (Weber M, et al., Neurosurgery 1990;27:106-12) were able to distinguish vasospasm from hyperemia in high velocity ranges using Lindegaard et al.'s approach (Lindegaard KF, et al., Stroke 1987;18:1025-30). The limitation of TCD velocimetry is that it does not measure microcirculation, but it summates large areas of blood flow and thus, may not "see" the injury or "hot spot." Additional concerns are that the TCD probe is not adequately fixed and may lose its target during ICU monitoring. Nursing procedures and surgical wound sites may introduce further interference.
Yet another technology which may be used for measuring CBF is laser doppler flowmetry (LDF). Under experimental conditions, LDF measurements have compared favorably with other methods for measuring CBF, including radiolabeled microspheres, hydrogen clearance, and quantitative autoradiography. LDF measures the movement of red blood cells (RBCs) within the microcirculation by using the Doppler shift undergone by coherent radiation generated by lasers. Typically, a fiberoptic probe structure is placed in contact with the tissue and guides incident light from the laser source to the tissue, as well as back-scattered light from the tissue to a photodetector within a flowmeter instrument. The flowmeter instrument processes the photodetector signal to elaborate a continuous voltage signal versus time which is linearly proportional to the real blood flow. Some examples of the probe structures, instrumentation, techiques, and signal processing are provided by U.S. Pat. Nos. 4,109,647, 4,476,875, and 4,596,254. It is well established that the laser emission does not alter microvascular blood flow. A salient attribute of LDF monitoring is that it provides continuous, real-time time signals that have a high spatial and temporal resolution. LDF is compact for bedside use and substantially less expensive than current alternatives which focus on CBF rather than 1CBF. LDF has been used for the evaluation of microcirculatory flow on a variety of tissues including skin, muscle, peripheral nerve, brain, and spinal cord.
Evidently, LDF provides a practical modality for use in an ICU environment for rapid, continuous capillary blood flow assessments with high spatial and temporal resolution. The primary focus of prior investigations and clinical measurements of CBF (e.g., using TCD, TDF, positron emission tomography (PET), single photon emission computed tomography (SPECT), xenon uptake) has been the larger cerebral conductance vessels. In the clinical arena, relatively little attention has been directed towards microvascular cerebral blood flow. The clinical utility of local CBF (1CBF) measurements using flowmetry is currently under investigation as a tool for evaluating cerebral perfusion, and there have been a number of useful LDF studies that focus on microvascular cerebral blood flow. These contributions have delineated important issues regarding the bedside utility of LDF monitoring, as well as the obstacles and limitations which must be overcome.
In 1987 Rosenblum et al. (Rosenblum BR, et at., J Neurosurg 1987;66:396-9) performed a single measurement of 1CBF from multiple cortical points surrounding a left parasagittal arteriovenous malformation before and after excision. During these measurements a hand-held probe was used and mean values in absolute flow units ml/100 g/rain) were obtained. Vessels larger than 100 .mu.m produced large aberrant flow values and movement artifacts were frequently encountered. There was fluctuations of flow attributable to vasomotion waves at 6-12 cycles/min.
Further experience with intraoperative LDF was reported by Fasano et al. (Fasano VA, et al., Acta Neurochir 1988;95:40-8) on 72 neurosurgical patients. A standard straight surface probe was placed on the surface of the brain and mounted on a self-retaining retractor in the operating room. By attenuating movement artifacts, it was possible to identify three rhythmic variations distinguished by high, medium, and low frequency components. The high component was synchronous with the heart rate; the medium component was synchronous with controlled ventilation; and the low frequency component reflected vasomotion. The effects of various stimuli including pharmacologically induced hypotension, infusion of mannitol, topical administration of nimodipine and papaverine, hypercapnia, and transient cervical carotid artery compression were studied. LDF measurements were also obtained before and after the removal of tumors, cysts, and hematomas.
In 12 patients with superficial brain tumors, Arbit et al. (Arbit E., et al., Neurosurgery 1989;24:166-70)used intraoperative LDF to measure 1CBF from normal cerebral cortex and tumor surfaces and compared these results with those obtained during induced hypertension and hypocapnia to evaluate autoregulation and CO.sub.2 reactivity. Flow readings were expressed in hHZ (100 Hz) as mean values. Despite transient interruption of controlled ventilation, the quality of the measured signals was impaired by movement artifacts and the presence of light in the operating room. Nevertheless, the authors emphasized that LDF monitoring provides continuous measurements of 1CBF as compared with the episodic data of positron emission tomography and xenon-133 clearance techniques.
In 1991 Mayevsky et al. (Mayevsky A., et al., In: Chance B, Datzir A, eds. Time-resound Spectroscopy and Imaging of Tissues, Los Angeles: SPIE 1991:303-13) introduced a multimodality probe that permitted the simultaneous recordings of LDF, NADH redox state, and the concentrations of K.sup.+, Ca.sup.2+, and Na.sup.+ in cerebral tissue. These signals were trended in a patient during and after temporary occlusion of a major intracranial vessel through the course of an aneurysm clipping. Clinical recordings were correlated with animal studies to investigate the relationship between metabolic and hemodynamic parameters during ischemic conditions.
Continuous postoperative LDF monitoring was carried out by Hashimoto et al. (Hashimoto T, et al., In: Frowen RA, Brock M, Klinger M. eds. Advances in Neurosurgery, vol 17. Berlin: Springer-Verlag, 1989;337-43) on 25 patients with aneurysmal subarachnoid hemorrhage (SAH). LDF probes were placed in the cortex at the time of operation and recordings were obtained intraoperatively and in the ICU that were correlated with epidural intracranial pressure (ICP), systemic arterial pressure (SAP), central venous pressure (CVP), and transcranial Doppler velocimetry (TCD). A special TCD flat probe was used for continuous monitoring of blood flow velocity. Three different signals were recorded from the LDF instrument: flow signal, velocity signal, and volume signal, which equals concentration of moving blood cells (CMBC). Variations of 1CBF were described that were synchronous with the TCD and ICP changes.
Additional experience with LDF monitoring in the ICU was reported by Meyerson et al. (Meyerson BA, et al., Nerosurgery 1991;29:750-5) on four comatose patients with head trauma (two cases), SAH (one case), and meningioma (one case). The authors used a special probe that is described below. Following intraoperative placement, the probe was tunneled under the scalp to reduce movement artifacts and permit continuous LDF monitoring for intervals of up to 13 days. 1CBF measurements were compared with both ICP variations and the clinical progress of the patient.
In connection with this prior art, special LDF probes have been developed for monitoring in the ICU; however, intraoperative insertion was required. Hashimoto et al. introduced an angular LDF probe containing a 1-cm-diameter steel disk for stability. The probe was positioned intraoperatively on the cortical surface. In the series of 25 patients described above, there were no complications using this probe. Potential complications of this technique include a cerebrospinal fluid fistula following removal of the probe, and interference with computerized tomographic and magnetic resonance examinations due to the steel disk.
A second composite LDF probe was introduced by Meyerson et al. This probe consists of a plastic connecting screw that joins a master probe and a thin disposable microprobe (500-750 .mu.m in diameter). The microprobe is applied to the cortical surface or fixed within cortical tissue at the end of neurosurgical procedures and is tunneled under the scalp for a distance of 10 cm to reduce movement artifacts. This permits continuous LDF monitoring for prolonged intervals. The plastic connecting screw facilitates optical coupling between the master probe and microprobe by maintaining close contact between the master probe and microprobe. A problem encountered by the present inventors in using this probe, however, is that the plastic connecting screw did not maintain constant optic coupling in agitated patients, resulting in an underestimation of flow signals. Also, although inexpensive, the disposable microprobes are fragile and occasionally break.
The prior art related to LDF probes and methods for measuring CBF, then, evince a number of limitations. For instance, all such probes and methods have been limited to intraoperative placement. Further, excessive compression of tissue by the surface probe is a potential cause of local ischemia. Conversely, incomplete contact between the probe and cortical surface can result in underestimating the flow signal. Movement artifacts are common with hand-held probes, and illumination of the cortical surface and the interposition of irrigation fluid and/or blood between the probe and cortical surface may interfere with LDF measurements. Moreover, correlation of LDF measurements with other continuously monitored cerebral physiological parameters (e.g., ICP) has relied on the use of multiple probes that probe different regions of cerebral parenchyma, thus resulting in increased invasion of cerebral tissue, and in inherently decreased correlation between measured parameters due to spatial separation.
In order to overcome these and other limitations of the prior art, and concomitantly, to provide LDF as a modality for measuring 1CBF, to provide novel modalities for assessing local cerebrovascular status, and further to provide novel methods for assessing patient status and clinical care, it is a general object of the present invention to provide an intracranial LDF probe for bedside insertion which provides for continuous monitoring of 1CBF.
A related object of the present invention to provide an improved apparatus for continuous monitoring of cerebrovascular microcirculation using laser Doppler flowmetry.
A further object of the present invention is to provide an intracranial probe, which may be inserted at the bedside and used for continuous monitoring of both cerebrovascular microcirculation and intracranial pressure in the same locus of cerebral tissue.
Another object of the present invention is to provide an intracranial multimodality probe to avoid the use of multiple probes to monitor multiple modalities.
Still another related object of the present invention is to provide an intracranial multimodality probe to minimize the extent and amount of cerebral tissue manipulation required to monitor multiple modalities.
Still a further object of the present invention is to provide, according to information from continuous monitoring of cerebrovascular microcirculation, improved and novel methods for monitoring and evaluating patient response to treatment maneuvers; and further, for assessing patient status earlier, thus allowing intervention when physiologic aberrations are a reversible point.
Yet another object of the present invention is to provide a system and method for continuous cerebral hemodynamic monitoring; and further, using the primary information obtained from continuous cerebral hemodynamic monitoring for the calculation and derivation of additional cerebrovascular parameters that may be vital to optimizing the patient condition.
Still another related object of the present invention is to provide a method for measuring and assessing physiological processes and parameters including: autoregulation, cerebral vascular resistance (CVR), and carbon dioxide (CO.sub.2) reactivity, according to measurement of microcirculation and pressure within the same locus of cerebral tissue.
Yet a further object of the present invention is to provide improved methods for titrating or targeting therapeutic maneuvers to optimize cerebral physiologic parameters; and contrawise, to understand when not to use therapeutic maneuvers that may otherwise be harmful.
Yet a further related object of the present invention is to provide a method and system for continuous monitoring of microcirculation parameters and metabolic parameters within the same locus of cerebral tissue.